Bone marrow transplantation (BMT) has been an increasingly successful treatment for patients with high-risk leukemia, lymphoma and other malignant and non-malignant diseases. Evaluation of BMT patients demonstrated an increased risk of Hodgkins disease after BMT, witih most cases related to Epstein-Barr virus. a separate evaluation of more than 3,000 children undergoing BMT found an over 40-fold risk of new cancers, with radiation and immune dysfunction identified as strong risk factors. Children and adolescents treated for Hodgkins disease experience significantly increased risks of a diverse spectrum of solid cancers for at least 20 years after initial treatment, and there is evidence that cancer risks continue among 25-year survivors. Children treated for germ- line Retinoblastoma (RB) experience very high risks of sarcomas, as well as melanoma and brain cancer. This cohort of RB patients continues to be followed to monitor their cancer risk, and RB patients who have developed melanoma are undergoing clinical examination for dysplastic nevi syndrome, lipomas, and mutations in melanoma susceptibility genes.In collaboration with the Genetic Epidemiology Branch, cancer risk is being determined in the relatives of patients with ataxia-telangiectasia to investigate whether persons heterozygous for AT are at increased risk of breast cancer in particular, as suggested by other studies. Sequencing of the ATM gene in patients and family members is also in progress. Second cancers following neutron exposure are being investigated in two cohorts to determine if neutrons are as or more effective in inducing second cancers as x and gamma rays. Cytogenetic evaluation of a subset of patients treated up to 17 years ago with neutrons indicated a large proportion of metaphases bearing structural chromosome aberrations. Two cohorts of patients in Slovenia and Israel, who received diagnostic I-131, are being evaluated for cancer incidence, in particular, thyroid cancer. Doses given in Slovenia were much higher than Israel and should provide an interesting contrast of the effects of I-131. - Human Subjects & Human Subjects: Interview, Questionaires, or Surveys Only